基于网络药理学探讨附子-细辛对高血压病的作用机制

Mechanism of action of Radix Aconiti Lateralis Preparata-asarum in treatment of hypertension based on network pharmacology

目的:基于网络药理学研究附子-细辛对高血压病的作用机制。方法:运用TCMSP数据库挖掘出附子-细辛的有效成分及药物预测靶点,采用5个生物信息数据库检索出高血压病的疾病预测靶标,构建药物靶点-疾病靶标交集,使用Cytoscape生物信息分析软件绘制"成分-靶点-疾病"中药调控网络,基于STRING数据库构建"药物-疾病"相关靶点的蛋白互作网络(PPI),并对其进行GO和KEGG的生物信息学分析。结果:通过生物利用度和类药性筛选得到附子-细辛的有效成分29个,对应药物靶点1807个,高血压病的疾病靶标8505个,构建的药物靶点-疾病靶标交集80个。与高血压病密切相关的GO富集条目91个,KEGG信号通路123条,主要涉及流体剪切应力与动脉粥样硬化、糖尿病并发症中的AGE-RAGE信号通路、白细胞介素(IL)-17信号通路、丝裂原活化蛋白激酶(MAPK)信号通路、PI3K-Akt信号通路等。结论:附子-细辛药对与高血压病密切相关,能够通过一条或多条通路协同发挥药效作用,考虑其可能是通过干预血液的流体剪切应力影响动脉粥样硬化与心血管重塑再生而实现的。

Objective:To investigate the mechanism of action of Radix Aconiti Lateralis Preparata-asarum in the treatment of hypertension based on network pharmacology.Methods:TCMSP database was used to obtain the effective constituents and drug prediction targets of Radix Aconiti Lateralis Preparata-asarum,and five bioinformation databases were used to obtain the disease prediction targets of hypertension to establish the intersection of drug targets and disease targets.Cytoscape bioinformation analysis software was used to plot the"constituent-target-disease"traditional Chinese medicine regulatory network,and the STRING database was used to establish a protein-protein interaction(PPI)network of"drug-disease"targets;gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)bioinformatics analyses were performed.Results:A total of 29 effective constituents of Radix Aconiti Lateralis Preparata-asarum were screened out based on bioavailability and drug-likeness,which corresponded to 1807 drug targets;there were 8505 disease targets for hypertension,and the intersection of drug targets and disease targets contained 80 targets.A total of 91 GO items and 123 KEGG signaling pathways were closely associated with hypertension,mainly involving fluid shear stress and atherosclerosis,the AGE-RAGE signaling pathway in diabetic complication,the interleukin-17 signaling pathway,the mitogen-activated protein kinase signaling pathway,and the PI3 K-Akt signaling pathway.Conclusion:The Radix Aconiti Lateralis Preparata-asarum drug combination is closely associated with hypertension and can exert a synergistic effect through one or multiple pathways,possibly by affecting atherosclerosis and cardiovascular remodeling and regeneration via intervention of the fluid shear stress of blood.